ABSTRACT An outbreak of serious pneumonia caused by a previously unknown viral pathogen, severe acute respiratory syndrome coronavirus (SARS-CoV-2), emerged in Wuhan, China in December 2019. Inadequate access to testing has limited our understanding of the extent of this new epidemic in the U.S. A cost effective accurate and rapid testing strategy is urgent to fill this gap. This administrative supplement to the UCSD Collaborative HIV Clinical Trials Unit (CTU) to screen all patient- facing research staff and a proportion of research participants is directly responsive to PA-18-591 and NOSI AI- 20-031 as it may allow safe resumption of key research services at our three U.S. Clinical Research Sites (CRSs) (UCSD Antiviral Research Center [AVRC] CRS, the University of Southern California [USC] CRS and the University of Colorado Hospital [UCH] CRS), serving persons with HIV (PWH) who may be at higher risk for COVID-19. Continuity of research coordinated with care is critical in progress toward ending the HIV epidemic without putting staff and participants at risk for COVID-19 acquisition in the research setting. No other local government or health systems are undertaking this approach. Our goal is to implement and evaluate a cost-effective screening approach to determine the prevalence of SARS- CoV-2 in asymptomatic research staff who are in direct contact with PWH and research participants being seen for study visits, identify new incident infections and potentially prevent asymptomatic carrier transmission of SARS-CoV-2 to PWH. This proposal is conceptually innovative in that it applies nucleic acid test (NAT) pooling techniques to save testing supplies, personal protective equipment and money to address an immediate need for increased testing. As there are no technical barriers, testing can start immediately. We will screen (1) direct care research personnel 3 days/week at UCSD (n=40) and weekly at USC (n=8) and UCH (n=20) for asymptomatic SARS-CoV-2 and (2) a subset of 10 research participants at each site every testing day. Self-collected nasal swab samples will be tested using a NAT pooling platform (UCSD AVRC CRS) or individual RT-PCR based commercial SARS-CoV-2 testing (USC and UCH CRSs). Our rationale is that by leveraging our CTU expertise in pooled NAT, the infrastructure capacity of the three CRSs and the San Diego Center for AIDS Research (CFAR), we will implement and evaluate a cost-effective screening approach to determine the prevalence of SARS-CoV-2 infection and SARS-CoV-2 immune response (i.e. seroprevalence) among direct care research staff and returning research participants (Aim 1) and to determine the test characteristics of pooled testing (UCSD AVRC) compared to individual RT-PCR based commercial SARS-CoV-2 testing (USC and UCH CRSs, Aim 2). Once validated, this approach can be deployed in other settings to help ensure safe return to work procedures or in high-risk settings such as healthcare workers in cancer or HIV clinics or nursing homes.